Neutrino Oscillations in Supersymmetry without Lepton number conservation and R-parity

With the on-shell renormalization scheme, we discuss neutrino masses up to one-loop approximation in the Supersymmetry without lepton number conservation and R-parity. Ii is shown that in this model with experimentally allowed parameters, $\Delta m^2_{23}, \Delta m^2_{12}$ and the mixing angles $|\sin\theta{23}|,|\sin\theta_{12}|$ which are consistent with the present observation values can be produced. We find that small neutrino mass ($\leq$ 1 eV) sets a loose constraint on the R-parity violation parameters in the soft breaking terms.Comment: 22 pages, plus one ps figure, accepted for publication in PR

RANKL Inhibition Through Osteoprotegerin Blocks Bone Loss in Experimental Periodontitis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141376/1/jper1300.pd

Report of the Regional Co-ordination Meeting for the North Sea and Eastern Arctic (RCM NS&EA) 2014

Report of the Regional Co-ordination Meeting for the North Sea and Eastern Arctic (RCM NS&EA) 2014 Swedish University of Agriculture Sciences (SLU Aqua) Lysekil, Sweden 08-12 September 2014The RCM NS&EA met in Lysekil (Sweden) between 8-12 September 2014. The main purpose of the RCM is coordinate the National Programmes (NP) of the Member States (MS) in the North Sea region for 2015

Report of the Regional Co-ordination Meeting for the North Sea and Eastern Arctic (RCM NS&EA) 2015

The RCM NS&EA met 31st August - 4th September 2015 at den Haag, Netherlands with 27 participants form 11 member states and autonomous regions attending, including representatives of ICES and the Commission. National correspondents from Spain, UK, Denmark, Lithuania, Germany, Sweden and the Netherlands were present. The meeting was co-chaired by Katja Ringdahl (Sweden) and Alastair Pout (Scotland). The RCM N&SEA considered the recommendations from the 11th Liasion meeting and summaries were presented of the work of expert groups and end users for the 2014-15 period to the plenary session of the meeting. The expert groups included WGCATCH, PGDATA, WKISCON2, WKRDB 2014-01, RDB–SC, STECF and the Zagreb meeting on transversal variables. ICES, as a main end user, provided feedback. A summary was presented of the progress in the regional coordination project (fishPi). This project involves over 40 participants from 12 members states from NS&EA, NA and Baltic regions, two external statistical experts, and ICES. The project has a wide scope of regional cooperation issues including sampling designs, data formats, code lists, PETS, stomach sampling, small scale and recreational sampling, and data quality software production. It has a budget of €400,000, and a one year time line and with a planned completion date of April 2016. A project with identical aims is running in paralleled in the Mediterranean and Black Sea regions The majority of the ToRs of the RCM NS&EA were addressed by three subgroups: one concerned with data analysis, one with the landing obligation, and one with issues particularly related to role and work of national correspondents

Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing

Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM) compared with vorinostat (VOR; EC50 = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 μM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART

A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4⁺ T-Cells to Recognition by Cytotoxic T-Lymphocytes

Resting CD4⁺ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8⁺ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8⁺ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8⁺ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8⁺ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8⁺ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam₃CSK₄. In contrast, we did not observe CD8⁺ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist ‘ALT-803’, an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8⁺ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8⁺ T-cells in HIV eradication strategies.United States. National Institutes of Health (AI111860

Rapid Seeding of the Viral Reservoir Prior to SIV Viremia in Rhesus Monkeys

The viral reservoir represents a critical challenge facing HIV-1 eradication strategies1–5. However, it remains unclear when and where the viral reservoir is seeded during acute infection and the extent to which it is susceptible to early antiretroviral therapy (ART). Here we show that the viral reservoir is seeded very early following mucosal SIV infection of rhesus monkeys and prior to systemic viremia. We initiated suppressive ART in groups of monkeys on days 3, 7, 10, and 14 following intrarectal SIVmac251 infection. Treatment on day 3 blocked the emergence of viral RNA and proviral DNA in peripheral blood and also substantially reduced levels of proviral DNA in lymph nodes and gastrointestinal mucosa as compared with treatment at later timepoints. In addition, treatment on day 3 abrogated the induction of SIV-specific humoral and cellular immune responses. Nevertheless, following discontinuation of ART after 24 weeks of fully suppressive therapy, virus rebounded in all animals, although animals treated on day 3 exhibited a delayed viral rebound as compared with animals treated on days 7, 10 and 14. The time to viral rebound correlated with total viremia during acute infection and with proviral DNA at the time of ART discontinuation. These data demonstrate that the viral reservoir is seeded very early following intrarectal SIV infection of rhesus monkeys, during the “eclipse” phase, and prior to viremia. This strikingly early seeding of the refractory viral reservoir raises important new challenges for HIV-1 eradication strategies